The long range objective of this research is to understand, on a mechanistic level, how drugs can be delivered through the skin while achieving therapeutic systemic blood levels in a controlled and enhanced manner. The method and manner by which transport enhancement will be investigated is by the application of a safe low voltage (iontophoresis) across excised human and nude mouse skin. The nude mouse skin will be evaluated as an alternative preclinical method for screening drug transport by iontophoresis. Both DC (constant current) and pulsed current modes of iontophoretic drug delivery will be investigated and compared. In particular, the skin's ion transport selectivity, the ion's transport pathway through the skin, the effects of enhanced charge transport on the skin, and the effects of the co- administration of iontophoresis and a model skin permeability enhancer on the skin will be determined. This information will allow the drug transport efficiencies and tissue alteration effects of constant current and pulsed iontophoresis to be assessed. An optimal iontophoretic delivery protocol will then be developed which maximizes drug delivery and minimizes tissue alteration. This protocol will be tested by using a model peptide drug and determining its iontophoretic transport across human skin.